Takotsubo cardiomyopathy is a transient heart failure characterized by apical ventricular ballooning following an acute physical or emotional stressor. The hallmark apical bulge with preserved basilar function resulted in the Japanese name ‘tako tsubo’, or octopus trap. We describe two cases of reversible myocardial dysfunction with unusual morphology consisting of midcavitary ballooning and hyperkinesis of apical and basilar segments reminiscent of a starfish, or ‘hitode’ in Japanese. These cases highlight the challenge in recognizing morphologically rare variants of stress cardiomyopathy, as well as the need for ongoing studies to elucidate their pathophysiologic underpinnings.
A 46-year-old woman was hospitalized following a fall from a bicycle. Symptoms included headache and difficulty with speech but no chest discomfort nor dyspnea. She had a history of amenorrhea, hypercalciuria, and early-onset osteoporosis. She did not have a history of anorexia nervosa, arrhythmia, nor seizures. Medications included hydrochlorothiazide, cabergoline, and an oral contraceptive. Initial evaluation revealed a thin woman with confusion and severe expressive aphasia. Computed tomography revealed a skull fracture associated with a large left temporal lobe contusion, subarachnoid bleed with edema, and slight midline shift. Serum troponin-I was elevated at 2.76 ng/ml (negative <0.03 ng/ml). Serum calcium, potassium, and magnesium levels were within normal limits. ECG revealed symmetric T-wave inversions in the anterior precordial leads. A transthoracic ECG revealed preserved left ventricular systolic function, with midcavitary circumferential dyskinesis (ballooning) and hyperkinesis of the apical and basilar segments, producing an unusual left ventricular morphology reminiscent of a starfish (Fig. 1a). Despite the patient’s presentation with elevated cardiac biomarkers, dynamic ECG changes, and segmental myocardial wall motion abnormalities, coronary angiography was not pursued because the distribution of myocardial dysfunction was anatomically incompatible with any known coronary vascular territory. ECG 2-weeks after discharge revealed complete resolution of wall motion abnormalities.
A 65-year-old man with a history of diabetes mellitus, hypothyroidism, chronic opioid dependency, and chronic obstructive pulmonary disease was hospitalized for hypoxic respiratory failure. Primary symptoms were dyspnea and near syncope, but no chest discomfort. Social history included ongoing tobacco use and recent life stressors, including a death in the family 2 days before hospitalization and a daughter who ran away from home. His only medication was oral methadone. His blood pressure was 94/58 mmHg and heart rate was 78 beats/min. Examination revealed normal heart sounds and mild bibasilar crackles. Initial ECG revealed sinus rhythm with T-wave inversions in the inferior leads. Cardiac troponin-I levels peaked 12 h after presentation at 9.46 ng/ml. Electrolytes, and thyroid stimulating hormone levels were within the normal range. Transthoracic ECG revealed mildly reduced systolic function and dyskinesia of the midventricular segments with preserved apical, basal, and distal segment contraction (Fig. 1b). Invasive coronary angiography was pursued given cardiac biomarker elevation and revealed a smooth, 40% ostial left main stenosis confirmed by intracoronary vascular ultrasound examination. There was no evidence of acute plaque rupture, dissection, nor epicardial coronary stenosis to explain the wall motion abnormalities. Repeat ECG showed resolution of wall motion abnormalities.
Stress cardiomyopathy has a myriad of precipitating triggers including toxic-metabolic, endocrine, trauma, and cardiorespiratory pathologies. Endocrine triggers include pheochromocytoma, hyperthyroidism, hypoglycemia, acute respiratory failure, and adrenal crisis 1–3. Head trauma and subarachnoid hemorrhage represent 2–3% of cases 4. Although both patients described above had identifiable triggers to explain their stress cardiomyopathy, these triggers do not explain their variant structure.
Other takotsubo variants include inverse (basal akinesis and apical hyperkinesis) 5, chestnut (hypokinesis of anterior and posterior basal walls and normal apex) 6, and sandglass (apical and basal akinesis with midventricular hyperkinesis) morphologies 7. In the two cases discussed, the left ventricular morphology bore resemblance to a starfish, with isolated, circumferential midventricular dyskinesia. One previous report of a patient with a pattern of ventricular dysfunction similar to that in the current case 1 also presented in the setting of subarachnoid hemorrhage 7. However, the vast majority of subarachnoid triggers do not result in a morphologic variant.
The endocrinopathies of both these patients involve calcium homeostasis, which is known to be dysfunctional in stress cardiomyopathy and heart failure in general 8,9. The first patient had a history of hypercalciuria and early-onset osteoporosis, which may have been indicative of primary idiopathic hypercalciuria. Calcium-ATPase serves as a major regulator of intracellular calcium transportation and dysfunction is implicated in primary idiopathic hypercalciuria 10. The second patient had underlying diabetes. Diabetes-associated left ventricular dysfunction is linked to abnormalities in calcium-regulated processes, including decreased sensitivity of cardiac myosin light chain to calcium and decreased Calcium-ATPase in the sarcoplasmic reticulum 11.
Stress cardiomyopathy is associated with abnormalities in calcium-ATPase and sarcolipan protein synthesis. In the acute phase, synthesis of sarcoplasmic calcium-ATPase decreases, which results in fewer enzymes to transport calcium against the cellular–sarcomere gradient. At the same time, sarcolipan synthesis increases and lowers the affinity of sarcoplasmic calcium-ATPase to calcium 9. Through these two mechanisms, intracellular calcium is increased and sarcomere calcium is decreased, resulting in both systolic and diastolic dysfunction 8. In contrast, calcium homeostasis during nonreversible heart failure is controlled by calcium–calmodulin-dependent protein kinase II, which affects cytoplasmic calcium levels through three different pathways. It also remains active after the initial stimulation has ceased, which gives it the name ‘memory molecule’ 8. Heart failure and stress cardiomyopathy are both affected by high plasma calcium levels resulting in similar physiology, but the second is less robust and may partially explain the reversibility of stress cardiomyopathy.
The two patients represented in this case report already had derangements of their calcium-ATPase secondary to their underlying endocrinopathies. Although the second insult to the sarcomeric calcium-ATPase may have been the trigger for stress cardiomyopathy, the starfish variant may result from the underlying cellular topography of the heart tissue favoring ballooning of nonapical segments.
In summary, these two cases of atypical patterns of myocardial dysfunction inconsistent with epicardial ischemia were likely triggered by subarachnoid hemorrhage and hypoxic respiratory failure 4. Although both patients showed abnormalities in calcium metabolism, the possible role of abnormal intracellular calcium handling in reversible myocardial dysfunction requires further study.
Stress-induced cardiomyopathy does not have defined diagnostic criteria; however, the Mayo Clinic standards require the absence of obstructive coronary artery disease or angiographic evidence of acute plaque rupture 12. Despite these proposed criteria, we elected not to perform catheterization in the first patient because of the patient’s age and the nonvascular distribution of the regional wall motion abnormality. Although this is a limitation of our report, the complete normalization of wall motion argues against irreversible injury due to myocardial infarction. Moreover, a simplified diagnostic standard that does not require invasive angiography could be developed and validated to identify those patients who truly warrant angiography. In addition, a system of nomenclature that encompasses the full spectrum of stress-induced cardiomyopathy syndromes would aid in the correct diagnosis and treatment. Finally, further investigation into predisposing conditions and pathophysiologic underpinnings of morphologically rare takotsubo variants seems warranted.
The authors thank Don Weule for assistance with the figure preparation.
Conflicts of interest
There are no conflicts of interest.
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